Background: Clinically significant portal hypertension (CSPH), causes a number of problems that is linked to decreased survival. Its diagnosis done by measuring the hepatic venous pressure gradient (HVPG). Although being invasive but gold standard one. In addition to fibrotic liver tissue remodeling, poor vasotonus control plays a role in the pathophysiology of portal hypertension (PH) in liver cirrhosis. Research on PH-affected animal models has shown that hepatic cGMP activity is reduced while systemic and splanchnic cGMP activity are reflectively elevated. These changes are part of what causes cirrhotic PH, which is characterised by hyperdynamic systemic and splanchnic circulation as well as profuse hepatic vascular resistance. This pathophysiological context implies that cGMP may serve as a PH marker. Objective: The aim of the current study was for evaluation of plasma level of cyclic guanosine monophosphate (cGMP) as a surrogate non-invasive biomarker of portal hypertension. Patients and methods: This case control study were performed at Ain Shams University Hospitals Inpatients and Outpatients' settings for one year. It included 40 cirrhotic patients with portal hypertension (Group I), 40 cirrhotic patients without PH (Group II), and 20 healthy controls (Group III). The following investigations were assessed for all study subjects: plasma cGMP, and abdominal US with portal vein duplex. Upper endoscopy was performed only for group I. Results: This study showed high statistically significant difference between the studied groups as regards plasma cGMP. Also, there was a statistically significant correlation between cGMP and portal vein diameter and splenic diameter in group I,butthere wasno statistically significant relation between plasma cGMP and presence of esophageal varices in group I. ROC curve for plasma cGMP to differentiate between cirrhosis cases with and without PH showed at cut off point > 53.6 plasma cGMP had a sensitivity of 95%, and specificity of 100% to detect portal hypertension in patient with liver cirrhosis. Conclusion: cGMP can be used as a noninvasive biomarker of portal hypertension. Also, cGMP at a cut off value >53.6 (with 99.4% accuracy) had 95% sensitivity, and 100% specificity. However, cGMP couldn't be used as a screening for esophageal varices.